The ligand binding signals to a wide variety of seven transmembrane cell surface receptors are transduced into intracellular signals through heterotrimeric G-proteins. Recently, there have been reports which show diverse coupling patterns of ligand-activated receptors to the members of Gq family alpha subunits. In order to shed some light on these complex signal processing networks, interactions between G alpha q family of G protein and neurokinin-2 receptor as well as muscarinic M1 receptor, which are considered to be new therapeutic targets in asthma, were studied. Using washed membranes from Cos-7 cells co-transfected with different G alpha q and receptor cDNAs, the receptors were stimulated with various concentrations of carbachol and neurokinin A and the agonist-dependent release of [3H]inositol phosphates through phospholipase C beta-1 activation was measured. Differential coupling of G alpha q family of G-protein to muscarinic M1 receptor and neurokinin-2 receptor was observed. The neurokinin-2 receptor shows a ligand-mediated response in membranes co-transfected with G alpha q, G alpha 11 and G alpha 14 but not G alpha 16 and the ability of the muscarinic M1 receptor to activate phospholipase C through G alpha q/11 but not G alpha 14 and G alpha 16 was demonstrated. Clearly G alpha q/11 can couple M1 and neurokinin-2 receptor to activate phospholipase C. But, there are differences in the relative coupling of the G alpha 14 and G alpha 16 subunits to these receptors.